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激素和激素和ARDSARDS Pathologically ARDS diffuse alveolar damagediffuse alveolar damagealveolar capillary leakagealveolar capillary leakage protein rich pulmonary oedema protein rich pulmonary oedema2激素和激素和ARDS3激素和激素和ARDSARDS病理分期渗出期:渗出期:ARDSARDS早期早期(7(7天天)纤维增生期:发病纤维增生期:发病7 7天以后进入纤维增生期天以后进入纤维增生期纤维化期:纤维化期:3 3周后则进入纤维化期。周后则进入纤维化期。三个病理阶段难以截然分开,常常交错存在,即三个病理阶段难以截然分开,常常交错存在,即ARDSARDS的早期就可以存在肺纤维增殖改变。的早期就可以存在肺纤维增殖改变。4激素和激素和ARDSEur Respir J Suppl 2003 Aug;42:57s-64s 5激素和激素和ARDS理论与临床实践的矛盾理论与临床实践的矛盾糖皮质激素糖皮质激素(简称激素简称激素)具有抑制炎症具有抑制炎症反应、减轻细胞因子对组织的损伤和反应、减轻细胞因子对组织的损伤和抑制纤维化等作用,抑制纤维化等作用,理论上来说,理论上来说,对各期对各期ARDSARDS激素治疗均应有较好的效激素治疗均应有较好的效果果 临床实践则是一个非常有争议的问题!临床实践则是一个非常有争议的问题!6激素和激素和ARDSSteroids in the treatment of clinical septic shockA prospective(PartI)and a retrospective(PartII)A prospective(PartI)and a retrospective(PartII)1、In Part I,172:either steroid or saline.43DXM,43MPS,86saline.2、double-blind,randomized,mortality:saline-treated:38.4%(33/86)steroid-treated:10.4%(9/86).Ann Surg.1976 Sep;184(3):333-417激素和激素和ARDSSteroids in the treatment of Steroids in the treatment of clinical septic shockclinical septic shockretrospective(Part II)retrospective(Part II)160 without steroid 168 with steroid Mortality:without steroid:42.5%(68/160)with steroid:14%(24/168)Ann Surg.1976 Sep;184(3):333-418激素和激素和ARDSEarly MPSS treatment for septic Early MPSS treatment for septic syndrome and the ARDS syndrome and the ARDS 时间:时间:1982 19851982 1985中心:中心:1919;受试者:;受试者:304 304 方法:随机、双盲、前瞻、安慰剂对照方法:随机、双盲、前瞻、安慰剂对照MPSS 30 mg/kg or PLA MPSS 30 mg/kg or PLA ARDSARDS:MPSS 50/152(32%)MPSS 50/152(32%);PLA 38/152(25%)PLA 38/152(25%)p=0.10p=0.10Chest 1988 Aug;94(2):448 9激素和激素和ARDSIneffectiveness of high-dose MPSS in preventing Ineffectiveness of high-dose MPSS in preventing Ineffectiveness of high-dose MPSS in preventing Ineffectiveness of high-dose MPSS in preventing parenchymal lung injury and improving mortality parenchymal lung injury and improving mortality parenchymal lung injury and improving mortality parenchymal lung injury and improving mortality in patients with septic shock in patients with septic shock in patients with septic shock in patients with septic shock 时间时间1983-19861983-198630 mg/kg 30 mg/kg,q6h,or PLA q6h,or PLA 受试者:受试者:8787ARDSARDS:MPSS 13MPSS 13;PLA 14PLA 14肺实质损伤无差异肺实质损伤无差异Am Rev Respir Dis.1988 Jul;138(1):62-810激素和激素和ARDS全身和局部的炎症全身和局部的炎症反应是反应是ALIALIARDSARDS发生和发展的重要发生和发展的重要机制机制血浆和肺泡灌洗液血浆和肺泡灌洗液中的炎症因子浓度中的炎症因子浓度升高与升高与ARDSARDS病死率病死率成正相关成正相关 大剂量糖皮质大剂量糖皮质激素既不能预激素既不能预防防ARDSARDS的发生,的发生,对早期对早期ARDSARDS也也没有治疗作用没有治疗作用11激素和激素和ARDS12激素和激素和ARDS糖皮质激素能抑糖皮质激素能抑制制ARDSARDS晚期持晚期持续存在的炎症反续存在的炎症反应,并能防止过应,并能防止过度的胶原沉积。度的胶原沉积。对晚期对晚期ARDSARDS可可能有保护能有保护对晚期对晚期ARDS(ARDS(患病患病7d 7d 24d)24d)应用糖皮质激素治疗应用糖皮质激素治疗并不降低并不降低60d60d病死率,但病死率,但可明显改善低氧血症和肺可明显改善低氧血症和肺顺应性,缩短患者的休克顺应性,缩短患者的休克持续时间和机械通气时问持续时间和机械通气时问 ARDSARDS发病发病14d14d应用糖皮应用糖皮质激素会明显增加病死率质激素会明显增加病死率13激素和激素和ARDSN Engl J Med,2006,354:16711684 14激素和激素和ARDSCorticosteroids in ARDSCorticosteroids in ARDS一个有争议的问题一个有争议的问题MP MP 缩短使用机械通气的时间,但也缩短使用机械通气的时间,但也出现神经肌肉乏力的副作用出现神经肌肉乏力的副作用目前尚无证据支持在早期或晚期目前尚无证据支持在早期或晚期ALI/ARDSALI/ARDS使用使用MP MP 15激素和激素和ARDSARDSARDS中晚期小剂量激素治疗效果中晚期小剂量激素治疗效果Eur Respir J Suppl.2003 Aug;42:57s-64s Loading Loading dosedose2mgkg2mgkg11 IV bolus followed by:IV bolus followed by:114d114d2mgkg2mgkg11dayday11 as as 0.5mgkg0.5mgkg11IV push every IV push every 6h6h1521d1521d1mgkg1mgkg11dayday11 as as 0.25mgk0.25mgkg g11IV push every IV push every 6h6h22282228#d#d0.5mgkg0.5mgkg11dayday11 as as 0.125mg0.125mgkgkg11IV push every IV push every 6h6h#:From days 2932,methylprednisolone was given in a single per os dose of 0.25mgkg1day1 for 2 days and 0.125mgkg1day1 for 2 days 16激素和激素和ARDS1980s trials1990s trialsTiming of ARDS2 days714 days(unresolved)Dosage120mgkg1day12mgkg1day1Duration1 dayAverage 30 daysUnderstanding of the HIR in ARDSMassive,short-livedProlonged,initial intensity affects durationUnderstanding of GCT in ARDSReversibility lost earlyReversibility lost with end-stage fibrosisGCTMassive,short-courseLower dose,prolonged until resolutionEur Respir J Suppl.2003 Aug;42:57s-64s 17激素和激素和ARDSARDSARDS中晚期小剂量激素治疗效果:中晚期小剂量激素治疗效果:延长激素的补充性治疗对延长激素的补充性治疗对ARDSARDS可能是有益的可能是有益的改善肺功能改善肺功能降低肺纤维化程度降低肺纤维化程度Eur Respir J Suppl.2003 Aug;42:57s-64s 18激素和激素和ARDS也许有一定的借鉴也许有一定的借鉴激素对多数重症激素对多数重症ARDSARDS治疗是必要的治疗是必要的综合治疗综合治疗l l周无效,炎症反应持续、或激素水平下周无效,炎症反应持续、或激素水平下降,可给予适当激素治疗,并应维持较长时间降,可给予适当激素治疗,并应维持较长时间19激素和激素和ARDS成功的疑惑成功的疑惑样本少样本少RCTRCT设计不够规范,严谨设计不够规范,严谨20激素和激素和ARDS20062006中国中国ARDSARDS指南推荐意见指南推荐意见 不推荐常规应用糖皮质激素预防和治不推荐常规应用糖皮质激素预防和治疗疗ARDS(ARDS(推荐级别:推荐级别:B B级级)21激素和激素和ARDS人感染高致病性禽流感人感染高致病性禽流感A(H5N1)A(H5N1)诊断和治疗建议诊断和治疗建议22激素和激素和ARDS目前尚未证实应用糖皮质激素对人禽流感患者预后有目前尚未证实应用糖皮质激素对人禽流感患者预后有任何有益的效果,尤其是大剂量激素还可诱发感染,任何有益的效果,尤其是大剂量激素还可诱发感染,故一般不推荐使用。故一般不推荐使用。糖皮质激素应用指征:糖皮质激素应用指征:(1 1)短期内肺病变进展迅速,出现氧合指数)短期内肺病变进展迅速,出现氧合指数300mmHg300mmHg,并有迅速下降趋势,并有迅速下降趋势(2 2)合并脓毒血症伴肾上腺皮质功能不全)合并脓毒血症伴肾上腺皮质功能不全23激素和激素和ARDS剂量?剂量?氢化可的松氢化可的松200mg/d200mg/d或甲基泼尼松龙或甲基泼尼松龙0.5-1mg/kg/d0.5-1mg/kg/d,在临床状况控制好转,在临床状况控制好转后,及时减量停用后,及时减量停用24激素和激素和ARDS指征的来源?指征的来源?非典期间的应用激素治疗的经验非典期间的应用激素治疗的经验若干研究报道休克伴相对肾上腺功能不若干研究报道休克伴相对肾上腺功能不全(尽管给予复苏治疗全(尽管给予复苏治疗SBP 90 SBP 60mg/d60mg/d给药途径:静脉注射或静滴给药途径:静脉注射或静滴维持时间:维持时间:3-53-5天天39激素和激素和ARDS小结小结激素用于激素用于ARDSARDS的治疗的治疗-权衡利弊权衡利弊原发病能否获得有效治疗是原发病能否获得有效治疗是ARDSARDS治疗成功的关键治疗成功的关键40激素和激素和ARDS谢谢 谢谢!41激素和激素和ARDS
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